Process-Related Impurities PRIs

A stability-specific-drug-substance-purity method must be able to separate any process-related impurity that is not purged or controlled prior to the final step and all of the API degradation products. Ideally, one would 

Experimental campaign bulk or in-process control samples (e.g., prior to recrystallization) are excellent sources of process-related impurities and are a vital component of the KPSS. Isolated fractions collected from a preparative or semi-preparative liquid chromatography (LC) system are also excellent KPSS samples. Sometimes small-scale synthesis of the impurity or degradant is possible and less time-consuming than the isolation techniques. 

During early stages of drug candidate development, raw materials and isolated process intermediates may be included in the finished goods essential peak set until the appropriate analytical and process-control strategies are implemented. Once the appropriate controls are in place as the candidate approaches commercialization, it may be possible to eliminate some of these components from the component set. 

Identity Tracking (NB ) Where Found Also In Purp Dag Grows on Stability Status Rationale 

Degradation nroduct 1 Dejpadation Yes Yes MUST Primary degradant controlled at DS finished goods stage 

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Process-Related Impurities (PRIs) e Isolated components Raw materials Isolated ntermediates Mother Liquors Un-recrystallized bulk lots Pur. Deg. or Stability samples Phase Equilibrium Supernatants Isolated Fractions Synthesis - Imouritv Grid... 

FIGURE I Impurity/degradant isolation and Identification process flowchart (RRT relative retention time PRI = process-related impurity). 

FIGURE 9 Impurity/degradant isolation and identification process flow chart. PRI, process-related impurity STD. standard RRT, relative retention time MW, molecular weight. 

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